Pagina's

Cannabinoids and nerve regeneration or neurogenesis

Most people and neurologist view nerves as 'copper ropes' conducting electricity. If the copper rope breaks, the nerve is damaged, and the damage is for the rest of our life. This creates great nihilism for therapeutic innovations. And even more disturbing, patients feel this metaphore is a desription of reality. The message patients often get from their neurologist is: nothing can be done, what is dead remains dead....

In 2010 an article on neuroregeneration takes quite another standpoint, a standpoint more in line with modern understanding of neuroplasticy and regeneration. The article started with the following remark: Until recently, the generation of neurons was thought to occur only during the embryonic period while the brain was considered relatively “stable” after birth. It is now clear that the mammalian brain is more plastic than previously perceived and has a remarkable ability to adapt to environmental stimuli or stress by modifying its structural and physiological characteristics. New neurons continue to be produced in two regions of the adult forebrain, the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ) lining the lateral wall of the lateral ventricle…

Neuroblasts and asterocytes

In particular, the authors emphasise in the conclusion: "bidirectional communication between astrocyte-like cells and neuroblasts has just been reported. Neuroblasts release GABA, which activates GABAARs on themselves and astrocyte-like cells while astrocyte-like cells release glutamate, which activates glutamate receptors on neuroblasts." [1]

We are only starting to scratch the surface of neuroregeneration. And there are probably many key players in our body, one of those is the cannabinoid receptor.

Cannabinoid receptor 1 and neurogenesis

In a recent animal experiment CBD (cannabidiol) improved neuroregeneration in the nerve system of adult mice. THC had no effect. [2] This is in line with other recent findings on the pluriform role of the CB 1 receptor. [3][4]

The authors concluded:

In this study we have shown that:

(1) exogenous cannabinoids THC and CBD differ in their effects on spatial learning and adult neurogenesis.

(8) in the absence of CB1 receptors, cell proliferation was increased and neuronal differentiation reduced.

CB 2 receptor activation and survival time in ALS mice

These findings are in line with data from a recent amyotrophic lateral sclerosis (ALS) model, the so called G93A-SOD1 mutant mice, one of the most well-characterized animal model of ALS. In this model endogenous cannabinoids are elevated in spinal cords of symptomatic mice. And treatment with cannabinoid partial agonists delays disease onset and prolongs survival of these mice. In this model the CB2, but not CB1, receptors are dramatically up-regulated in spinal cords in a temporal pattern paralleling disease progression. Treatment with the selective CB2 agonist AM-1241, increased the survival interval after disease onset by 56%. [5]

CB2 receptor and microglia-progenitor cells interaction

Activation of CB2 receptor on microglia suppresses of the proliferation and activation of microglia. Therefore there is potential for the anti-inflammatory properties of cannabinoid agonists or precursors to treat disorders that involve heightened microglia activity, such as neuropathy. Even more intersting and in line with the above findings, it was stated that CBII receptors may result in an increase in proliferation and affect migration of neuro-progenitor cells. Therefore, it is possible that CBII agonists may assist in the treatment of neuropathologies by increasing neurogenesis[6]

This all is quite interesting, and it also brings forth new elements for the understanding we have so far about the neuroprotective properties of a cannabinoid mimetic, on the market as a food supplement, N-palmitoyl-ethanolamine (PEA). [7]

PEA and nerve regeneration?

PEA is an endogenous cannabimimetic compound, and anandamide analogue, which exert potent anti-inflammatory and analgesic effects in experimental models. Recently, three separate studies indicating that PEA concentrations are significantly increased during three different inflammatory and neuropathic conditions, two of which have been assessed in humans, and one in a mouse model. For instance, PEA levels in biopsies from patients with ulcerative colitis were found to be 1.8-fold higher (P<0.05, N=8-10) than those in healthy subjects.[8]

In neuropathic states low grade inflammation is one of the hall marks, and recently an Italian group (Bassiotta et al, 2010) demonstrated that 2 times 600 mg PEA daily is capable of not only reducing neuropathic pain but also improving nerve conduction. In light of the above findings, the question whether PEA as a CB 1 and CB2 agonist has neurogenic properties in the peripheral nerve system.